Genetic Variant C16orf74:p.Ser21del (chr16-85710272-GGCT-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_206967.3(C16orf74):c.61_63delAGC(p.Ser21del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000652 in 1,488,054 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00072 ( 0 hom. )

Consequence

C16orf74
NM_206967.3 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.57

Publications

1 publications found

Variant links:

Genes affected

C16orf74 (HGNC:23362): (chromosome 16 open reading frame 74)

C16orf74 links:

ENSG00000287125 (HGNC:):

ENSG00000287125 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_206967.3

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206967.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C16orf74	NM_206967.3	MANE Select	c.61_63delAGC	p.Ser21del	conservative_inframe_deletion	Exon 3 of 4	NP_996850.1	Q96GX8-1
C16orf74	NR_161452.1		n.292_294delAGC		non_coding_transcript_exon	Exon 4 of 5
C16orf74	NR_161454.1		n.228_230delAGC		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C16orf74	ENST00000284245.9	TSL:1 MANE Select	c.61_63delAGC	p.Ser21del	conservative_inframe_deletion	Exon 3 of 4	ENSP00000284245.3	Q96GX8-1
C16orf74	ENST00000602583.5	TSL:1	c.25_27delAGC	p.Ser9del	conservative_inframe_deletion	Exon 1 of 2	ENSP00000473536.1	Q96GX8-2
C16orf74	ENST00000602675.5	TSL:1	c.-81_-79delAGC		5_prime_UTR	Exon 3 of 4	ENSP00000473306.1	R4GMV5

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00766

AC:

850

AN:

111014

AF XY:

0.00735

show subpopulations

Gnomad AFR exome

AF:

0.0110

Gnomad AMR exome

AF:

0.0108

Gnomad ASJ exome

AF:

0.00399

Gnomad EAS exome

AF:

0.0141

Gnomad FIN exome

AF:

0.00588

Gnomad NFE exome

AF:

0.00737

Gnomad OTH exome

AF:

0.00577

GnomAD4 exome

AF:

0.000718

AC:

959

AN:

1335956

Hom.:

AF XY:

0.000833

AC XY:

550

AN XY:

660300

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00125

AC:

AN:

27270

American (AMR)

AF:

0.00592

AC:

152

AN:

25656

Ashkenazi Jewish (ASJ)

AF:

0.00117

AC:

AN:

23070

East Asian (EAS)

AF:

0.00186

AC:

AN:

31804

South Asian (SAS)

AF:

0.00222

AC:

154

AN:

69250

European-Finnish (FIN)

AF:

0.00214

AC:

AN:

43856

Middle Eastern (MID)

AF:

0.000551

AC:

AN:

5440

European-Non Finnish (NFE)

AF:

0.000384

AC:

405

AN:

1054304

Other (OTH)

AF:

0.000561

AC:

AN:

55306

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.257

Heterozygous variant carriers

133

267

400

534

667

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67982

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00365

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.6

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over